Background and aims: While androgen deprivation therapy (ADT) has been associated with insulin resistance and increased diabetes risk, there have been few controlled prospective studies. We hypothesized that ADT influences insulin resistance indirectly, via effects on body composition,.
Methods: This prospective case-control study recruited 63 men with localised prostate cancer, 29 cases (newly commencing ADT) and 24 controls (not receiving ADT), matched for age and radiotherapy. Fat mass, lean mass and visceral adipose tissue (VAT) was measured by DEXA and insulin resistance was estimated from the updated Homeostasis Model Assessment (HOMA2-IR). Using a mixed model, the mean adjusted differences (MAD) between groups from 0 to 12 months are reported.
Results:
Compared with controls, fat mass increased in men receiving ADT by 3529.5g [2012, 5047], p<0.02 and lean mass decreased by 1491g [181, 2801], p<0.02. VAT was unchanged (p=0.66). HOMA2-IR increased in the ADT group compared with controls (mean adjusted difference 0.59 [0.24, 0.94], p=0.02). HbA1c levels and prevalence of diabetes was unchanged. Increase in HOMA2-IR was predicted by a change in testosterone (p<0.001) or change in fat mass (p<0.001) in separate models, which were also strongly associated with each other (p>0.001). HOMA2-IR was not predicted by lean mass. In a combined model with testosterone and fat mass only, fat mass change (p<0.001) remained a significant predictor of HOMA2-IR, but not change in testosterone (p=0.63).
Conclusion:
These findings suggest that ADT may increase insulin resistance indirectly, via body composition changes, rather than via effects of testosterone withdrawal. This occurs in the absence of obvious changes in VAT, suggesting that there may be deleterious effects of subcutaneous fat. This reinforces the importance of implementing lifestyle measures to prevent obesity in men commencing ADT.